IL-12/IL-12R system in multiple sclerosis

IL-12/IL-12 receptor (IL-12R) system orchestrates the Th1 pathway of the im mune system by maintaining one of the major bridges between innate and adap tive immune responses. Here, we studied both sides of this system in patien ts with multiple sclerosis (MS) and in controls. MS patients displayed elev ated IL-12R beta1 and IL-12R beta2 expression on PHA-activated T cells comp ared to healthy subjects. Higher percentages of IL-12R beta1 and IL-12R bet a2 positive T cells in cerebrospinal fluid (CSF) compared to blood were obs erved both in MS and other neurological diseases (OND). In contrast, number s of IL-12 secreting blood mononuclear cells (MNC) were similar in MS and c ontrols. The functional importance of high IL-12R beta2 in MS was underline d by the finding that IL-12 stimulated IFN-gamma production and proliferati on of PHA-activated T cells correlated with levels of IL-12R beta2. express ion. Our data indicates a dysregulation of the IL-12/IL-12R system in MS. I t is suggested that even in the absence of increased IL,-12 levels, the net effect of IL,-12 might be augmented in MS by elevated expression of its re ceptor. (C) 2001 Elsevier Science B.V. All rights reserved.